The Immuno-oncology Program has traditionally represented a major focus of basic scientific strength at AECC and at the last CCSG review was rated as excellent. Since that time this program has greatly increased its cancer focus through changes in membership, the evolution of research of existing members and the recruitment of new faculty, several of whom are physician-scientists, to the College and this Program. These changes were a natural evolution program member's research and a response to the previous summary statement. The goals of the Immuno-oncology program are: 1) To determine how defects in the targeting of the genomic instability of immunoglobulin genes required for the generation of antibody diversity lead to the mutations and translocations that cause B cell lymphomas and to search for ways to prevent such errors. One objective is to develop therapeutics targeted specifically to molecularly distinct Bcell lymphoma variants. 2) To better understand how antigen is presented to T cells and how to manipulate that process to increase the immunogenicity of tumors and cancer vaccines. 3) To develop and apply new immune therapies with a focus on radio-immunotherapy and vaccines to viral-induced tumors. Translational accomplishments include the development of a anti-melanin-mAb-radionuclide therapeutic, which emerged from studies on fungal melanin, that will enter clinical trials in 2007. Studies focused on the role of Bcl6 in the pathogenesis of diffuse large B cell lymphoma have identified a peptide inhibitor of the interaction between this protein and its corepressor. This peptide is active pre-clinically, and is being further developed in preparation for transition to a pharmaceutical company for clinical studies. The recruitment of two secondary members to this program has linked clinical and basic investigators who study vaccines within the context of clinical trials focused on the treatment of cervical neoplasia and other solid tumors. There are currently 16 program members from 11 departments, of whom 11 are primary members, supported by 6 NCI ($1.45M Direct) and 7 other NIH grants. Since the last CCSG review there have been 176 cancer-relevant research papers by members of this program of which 7% represent intraprogrammatic, and 19% represent interprogrammatic collaborations.